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Nucleoside reverse transcriptase inhibitors impair endothelium-dependent relaxation by increasing superoxide
Roy L Sutliff1, Sergey Dikalov, Daiana Weiss
1Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, USA. rsutlif@emory.edu
American Journal of Physiology. Heart and Circulatory Physiology
|October 22, 2002
Summary
Nucleoside reverse transcriptase inhibitors (NRTIs) used for HIV treatment increase superoxide levels, impairing blood vessel function and potentially contributing to cardiovascular issues.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Toxicology
Background:
- Nucleoside reverse transcriptase inhibitors (NRTIs) are crucial in managing HIV/AIDS, but are linked to tissue toxicities like cardiomyopathy.
- Understanding NRTI-induced vascular dysfunction is vital for mitigating adverse cardiovascular effects.
Purpose of the Study:
- To investigate the impact of NRTIs on vascular function.
- To elucidate the mechanisms underlying NRTI-associated cardiovascular complications.
Main Methods:
- Isolated mouse aorta segments were used for functional assays (contraction and relaxation) after exposure to zidovudine (AZT) or stavudine.
- Dihydroethidium staining and electron spin resonance were employed to measure superoxide levels in vascular tissues and endothelial cells.
Main Results:
- AZT and stavudine impaired endothelium-dependent relaxation in mouse aorta.
- AZT treatment significantly increased superoxide levels in both isolated vessels and cultured endothelial cells.
- The free radical scavenger tiron restored endothelium-dependent relaxation in AZT-exposed vessels.
Conclusions:
- NRTIs impair vascular endothelial function by elevating superoxide levels.
- NRTI therapy may contribute to cardiovascular complications in patients with acquired immunodeficiency syndrome.